Rheumatoid arthritis is chronic inflammatory disease characterized by multiple arthritis. In initial stage an inflammation occurs in synovial membrane covering a joint but it spreads across the surrounding cartilages and bones to destroy and modify the joint. Besides joint, other symptoms out of the joint comprise anemia, Sjogren's syndrome, subcutaneous nodule, pulmonary fibrosis, vasculitis, skin ulcer as disease able to do systemic invasion.
The exact cause of rheumatoid arthritis has not found yet, but autoimmunity has been known as a major mechanism thereof. The autoimmunity means a disorder of an immune system attacking itself rather than protecting from outside. Generally a genetic factor and an infection of bacteria or virus have been regarded as the cause of rheumatoid arthritis. Rheumatoid arthritis has been commonly known as the disease which easily occurs after getting stressed physically or psychologically. In other words, rheumatoid arthritis is an inveterate autoimmune disease involving a swelling, an inflammation, stiff and a pain in a joint and showing a systemic multiple arthritis symptom in whole body. In other words, it means a systematic disease that the body regards itself as nonself, attacks itself based on a defect of recognizing self-nonself and generates an abnormal immune response making an inflammation of connective tissue.
Degenerative arthritis, namely osteoarthritis means a disease. When an aging and degeneration arise in chondrocytes consisting a cartilage, synthesizing type II collagen and proteoglycan are inhibited and simultaneously creating inflammatory cytokines comprising interleukin-1β and tumor necrosis factor-α are induced and then a synthesis and an activity of matrix metalloproteinase (MMP) which degrades joint matrix are increased so that the destructed cartilage tissue causes the disease.
Furthermore, rheumatoid arthritis is worsened by an acceleration of degrading joint matrix when much more MMP synthesis is induced by production of a nitrogen monoxide causing a synthesis of self-amplified inflammatory cytokines. At the same time, the inflammatory cytokines induce an inflammation at arthritis by increasing production of prostaglandin E2 which is a lipid metabolite.
As therapies for chronic joint rheumatism, anti-inflammatory steroid (e.g. prednisolon), non-steroidal anti-inflammatory drug (e.g. indomethacin, aspirin), immunosuppressant (e.g. cyclosporine A, tacrolimus (FK506), methotrexate, cyclophosphamide, azathioprene), disease modification anti-rheumatism drug (e.g. gold salt reagent) are used. Anti-inflammatory drugs control an inflammation and reduce a pain and swelling, but it is difficult to inhibit a progress of disease. Therefore, most of drugs simply alleviate symptoms or delay a progress of a disease and also have a probability of expressing side effect in long-term administration so no drug can be said enough to be satisfiable.
On the other hand, drugs for treatment of rheumatoid arthritis could be classified based on major mechanisms of a reduce of an inflammation, a delay of a disease progress and a decline of a uric acid concentration, and many drugs for treatment of neural joint reduce an inflammation. The inflammation is a pathological progress causing a pain, an edema, a fever, a seizure and a stiff, and drugs to ease the inflammation rapidly comprise non-steroid anti-inflammatory drug comprising aspirin and steroid anti-inflammatory drug comprising cortisone.
Non-steroid anti-inflammatory drug has an effect to relieve an inflammation and to ease neural joint by reducing a pain, but the drug is prohibited for a person who has an active peptic ulcer and a history of bleeding in stomach area because the drug may cause a gastro enteric trouble and a stomachache. Steroid anti-inflammatory drug is not used commonly because the drug has a severe side effect comprising a weight gain and a hypertension compared to its effectiveness. Particularly, steroid anti-inflammatory drug is irrelevant to a radical therapy and the drug may lead to over-use because of a reduction in a pain temporarily, so there is need to care to use the drug which may cause a destruction of neural joint and an aggravation of a disease.
Therefore, because existing therapies used to treat arthritis have a limited effectiveness of treatment and also involve a side effect, the existing therapies have a problem that they are not be able to be used in the long term. So, new therapy that can solve problems in the existing therapies has been needed.